chr18-3450206-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003244.4(TGIF1):​c.-284A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00502 in 1,378,062 control chromosomes in the GnomAD database, including 261 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 146 hom., cov: 32)
Exomes 𝑓: 0.0025 ( 115 hom. )

Consequence

TGIF1
NM_003244.4 5_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.363
Variant links:
Genes affected
TGIF1 (HGNC:11776): (TGFB induced factor homeobox 1) The protein encoded by this gene is a member of the three-amino acid loop extension (TALE) superclass of atypical homeodomains. TALE homeobox proteins are highly conserved transcription regulators. This particular homeodomain binds to a previously characterized retinoid X receptor responsive element from the cellular retinol-binding protein II promoter. In addition to its role in inhibiting 9-cis-retinoic acid-dependent RXR alpha transcription activation of the retinoic acid responsive element, the protein is an active transcriptional co-repressor of SMAD2 and may participate in the transmission of nuclear signals during development and in the adult. Mutations in this gene are associated with holoprosencephaly type 4, which is a structural anomaly of the brain. Alternative splicing has been observed at this locus and multiple splice variants encoding distinct isoforms are described. [provided by RefSeq, Jul 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
Variant 18-3450206-A-T is Benign according to our data. Variant chr18-3450206-A-T is described in ClinVar as [Benign]. Clinvar id is 1232556.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0834 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TGIF1NM_003244.4 linkuse as main transcriptc.-284A>T 5_prime_UTR_variant 1/3 ENST00000343820.10
LOC124904237XR_007066269.1 linkuse as main transcriptn.125+326T>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TGIF1ENST00000343820.10 linkuse as main transcriptc.-284A>T 5_prime_UTR_variant 1/31 NM_003244.4 P1Q15583-2

Frequencies

GnomAD3 genomes
AF:
0.0251
AC:
3813
AN:
152140
Hom.:
145
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0856
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0115
Gnomad ASJ
AF:
0.00288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00103
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000441
Gnomad OTH
AF:
0.0210
GnomAD4 exome
AF:
0.00252
AC:
3087
AN:
1225804
Hom.:
115
Cov.:
29
AF XY:
0.00230
AC XY:
1358
AN XY:
591198
show subpopulations
Gnomad4 AFR exome
AF:
0.0858
Gnomad4 AMR exome
AF:
0.00780
Gnomad4 ASJ exome
AF:
0.00230
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000336
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000244
Gnomad4 OTH exome
AF:
0.00646
GnomAD4 genome
AF:
0.0251
AC:
3829
AN:
152258
Hom.:
146
Cov.:
32
AF XY:
0.0246
AC XY:
1829
AN XY:
74456
show subpopulations
Gnomad4 AFR
AF:
0.0857
Gnomad4 AMR
AF:
0.0114
Gnomad4 ASJ
AF:
0.00288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00103
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000441
Gnomad4 OTH
AF:
0.0208
Alfa
AF:
0.000863
Hom.:
0
Bravo
AF:
0.0279
Asia WGS
AF:
0.00866
AC:
30
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxOct 30, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
CADD
Benign
12
DANN
Benign
0.72
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs7233448; hg19: chr18-3450204; API